219 Molecular diagnostics of ichthyoses using genodermatoses-dedicated next generation sequencing panel in polish patients

Abstract

Mental disorders participate in the development of psoriasis as predisposing factors; a correlation of dermatological diseases with pathological anxiety and stress was shown. The aim of this study is to find the associations between SNV in genes COMT (rs4680), DBH (rs141116007), CCKAR (rs1800857), CCKBR (rs1805002), and psoriasis. In our study The c 2 test revealed an association with psoriasis only for the COMT gene, which encodes catechol-O-methyltransferase. Results of polygenic analysis also showed a significant influence of gene polymorphism COMT (rs4680) in the development of psoriasis. The carrying of both alleles in combinations with alleles of other genes forms the strongly associated patterns. Besides, the G allele, both alone and in combination with other genes and / or A allele, forms markers of strong predisposition to the disease. The AA genotype in the meantime is protective. This indicates the dominant manifestation of the G allele in the case of psoriasis. The association of GA genotype of COMT gene with psoriasis found in our study has no direct explanation of its functional activities. The most interesting hypothesis, which could explain the effect of the GA heterozygote of the COMT gene on the pathogenesis of psoriasis, from our point of view, is the possibility of changing the activity of the heterodimer. Thus, it was shown that COMT enzyme can exist in three forms: a monomer, a membrane-bound monomer and a dimer. The structure of proteins COMT 158Val and COMT 158Met is different, which results in different affinity to substrates and different stability of the enzyme. Thus, patients with psoriasis have an increased excretion of adrenaline in stressful situations.

Genodermatozy – patogeneza i diagnostyka molekularna

“…Alternatywnie, u chorych z podejrzeniem rybiej łuski sprzężonej z chromosomem X wykonać można analizę ilościową MLPA (multipleksowa amplifikacja sond zależna od ligacji), która umożliwia wykrycie delecji genu STS (kodującego sulfatazę steroidową) W pozostałych sytuacjach analiza NGS powinna być proponowana jako molekularne badanie pierwszego rzutu. W przypadku diagnostyki MeDOC i EB, wykrywalność mutacji z wykorzystaniem NGS jest wysoka i wynosi ponad 80% [40,44]. W większości ośrodków na świecie rutynowo wykonuje się analizę panelową, obejmującą wyłącz-nie fragmenty kodujące wybranych genów lub eksomową (WES, ang.…”